Amelioration of systemic autoimmune disease by the stimulation of apoptosis-promoting receptor Fas with anti-Fas mAb.
Fas antigen (Fas) is a cell surface receptor molecule that mediates apoptosis-inducing signals into activated and/or autoreactive peripheral T and B cells by stimulation with Fas ligand or agonistic anti-Fas mAb. The i.p. administration of the hamster anti-mouse Fas mAb RK-8, which induced apoptosis both in vivo and in vitro, did not kill adult mice, whereas those given another hamster anti-mouse Fas mAb Jo2 rapidly die of fulminant hepatitis with hemorrhage. Here, we report that MRL-gld/gld mice thoroughly recovered and/or were prevented from glomerulonephritis, arthritis, sialadenitis, vasculitis and lymphoadenopathy after receiving a single administration of the agonistic anti-mouse Fas mAb RK-8. The serum levels of autoantibodies were decreased after the administration. All the therapeutic effects of RK-8 persisted for >6 months. These findings suggest that the systemic administration of agonistic anti-Fas mAb without fulminant hepatitis-inducing activity is a useful therapeutic strategy for treating systemic autoimmune disease.
Nishimura-Morita
Y
Y
The Pharmaceutical Basic Research Laboratories, JT Inc., Yokohama, Japan.
Nose
M
M
Inoue
T
T
Yonehara
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology; D006224:Cricetinae; D053222:Fas Ligand Protein; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008168:Lung / Q000187:drug effects; D008206:Lymphatic Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D012469:Salivary Glands / Q000187:drug effects; D013163:Splenomegaly / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019014:fas Receptor